Autoantigen-specific T cell proliferation induced by the ribosomal P2 protein in patients with systemic lupus erythematosus.

Abstract

A role for helper T cells in the induction of pathogenic lupus autoantibodies is increasingly supported by data from studies of murine lupus and patients with systemic lupus erythematosus (SLE). However, the poor in vitro function of SLE T cells has hampered the identification and characterization of autoantigen-specific T cells. We used recombinant fusion proteins to study the T cell proliferative response of 31 lupus patients and 27 healthy subjects to a well-characterized SLE autoantigen, the ribosomal P2 protein. Although PBMC from SLE patients showed marked impairment in the proliferative response to the common recall antigen tetanus toxoid when compared with normal subjects, a significantly greater proportion of SLE patients (32%) than normal individuals (0%) showed a T cell response to a recombinant P2 fusion protein. When the SLE patients were subgrouped according to the presence of serum anti-P autoantibody, 7 of 10 anti-P antibody-positive patients, but 0 of 20 anti-P antibody-negative SLE patients, demonstrated > 2,000 cpm [3H]thymidine incorporation and a P2 stimulation index > 5. The specificity of the T cell proliferative response for the P2 protein was confirmed by studies using a second recombinant human P2 fusion protein and by the specific activation of P2-primed T cells by recombinant P2 in secondary cultures. Moreover, the T cell proliferative response to the P2 autoantigen was mediated by CD4-positive T cells and was inhibited by anti-MHC class II antibodies. These data demonstrate the presence of autoantigen-specific T helper cells in patients with SLE and suggest that these T cells drive the production of autoantibodies by B lymphocytes. (J. Clin. Invest. 1994.94:345-352.)

Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.

“…T cells reactive with autoantigens targeted by autoantibodies were identified in patients with various systemic or organ-specific autoimmune diseases (8)(9)(10). These autoantigen-specific T cells almost always had a CD4 ϩ phenotype, known as helper T cells.…”

Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes.

“…1 Recent investigations have supported the important roles of defined autoantigens, as well as autoantigen-specific T helper (T h ) cells, in the induction of the autoantibodies that comprise these pathogenic immune complexes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). As in specific immune responses to most antigens, autoantibody production is likely to depend on interaction of self antigen with B cell surface immunoglobulin receptors and the receipt of B cell surface signals mediated by direct interaction with the T h cell surface, as well as T h cell-derived cytokines (11,12).…”

Interleukin-10 promotes activation-induced cell death of SLE lymphocytes mediated by Fas ligand.

“…While the character of these autoantibodies suggests a requirement for T helper cells, only recently have autoantigen-specific, CD4-positive T cells been demonstrated in these patients (2,3). Many studies indicate chronic and ongoing triggering of SLE T cells in vivo, as evidenced by increased expression of activation markers such as Fas, CD45 isoforms, and adhesion molecules (4-7), as well as by increased secretion of the cytokines, IL-6 and IL-10 (8-13).…”